US2009221611A1PendingUtilityA1
Fused Triazole Tachykinin Receptor Antagonists
Est. expiryJan 11, 2026(expired)· nominal 20-yr term from priority
A61P 7/12A61P 43/00A61P 25/24A61P 25/22A61P 29/00A61P 25/04A61P 1/08A61P 11/00A61P 1/04C07D 471/04A61P 21/00A61P 13/10
42
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Claims
Abstract
The present invention is directed to certain fused triazole compounds which are useful as neurokinin-1 (NK-I) receptor antagonists, and inhibitors of tachykinin and in particular substance P- The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.
Claims
exact text as granted — not AI-modified1 . A compound of the formula I:
wherein:
R is selected from the group consisting of:
(1) C 1-3 alkyl,
(2) aryl, selected from phenyl and naphthyl,
(3) heteroaryl, or N-oxide thereof wherein the heteroaryl is an aromatic monocyclic of 5 or 6 atoms having 1, 2 or 3 heteroatoms selected from the group consisting of N, S and O,
(4) heterocyclic ring, wherein the heterocycle is a non-aromatic ring of 4, 5 or 6 atoms having 1, 2 or 3 heteroatoms selected from the group consisting of N, S and O,
(5) cyclohexane,
(6) —C 1-3 -aryl,
(7) —C 1-3 alkyl-heteroaryl,
(8) —C 1-3 alkyl-heterocycle,
(9) —C 1-3 alkyl-cyclohexane,
(10) hydroxy,
(11) —C(O)—O—R 1 ,
(12) C 1-3 alkyl-C(O)—O—R 1 and,
(13) AR, wherein AR is selected from
wherein choices (1) through (8) are optionally substituted with 1 or 2 groups selected from
(1) oxo,
(2) CH 3 ,
(3) OH,
(4) —CH(OH)CH 3 ,
(5) —OCH 3 ,
(5) —C(O)C 1-3 alkyl,
(6) —(O)—O—C 1-4 alkyl,
(7) —C(O)NHCH 3 ,
(8) C(O)N(CH 3 ) 2 ,
(10) —NH 2 ,
(11) —N(CH 3 ) 2 ,
(12) AR′, wherein AR′ is selected from the group consisting of
R 1 is hydrogen or C 1-3 alkyl;
R 2 is hydrogen, hydroxyl, methyl, —NH 2 or —NHC(O)—O—C 1-4 alkyl;
X, Y and Z are independently selected from the group consisting of:
(1) hydrogen,
(2) halo, and
(3) C 1-3 alkyl;
or a pharmaceutically acceptable salts thereof and individual enantiomers and diastereomers thereof.
2 . A compound according to claim 1 of formula Ia:
and pharmaceutically acceptable salts thereof and individual enantiomers and diastereomers thereof.
3 . A compound according to claim 2 wherein
the heterocycle of R is selected from the group consisting of
4 . A compound according to claim 2 wherein
the heteroaryl of R is selected from the group consisting of
5 . A compound according to claim 2 wherein X is fluorine, Y is hydrogen, and Z is hydrogen.
6 . A compound according to claim 2 wherein X is methyl, Y is hydrogen, and Z is hydrogen.
7 . A compound according to claim 2 wherein
R is selected from the group consisting of:
(1) heteroaryl, or N-oxide thereof wherein the heteroaryl is an aromatic monocyclic of 5 or 6 atoms having 1, 2 or 3 heteroatoms selected from the group consisting of N, S and 0,
(2) heterocyclic ring, wherein the heterocycle is a non-aromatic ring of 4, 5 or 6 atoms having 1, 2 or 3 heteroatoms selected from the group consisting of N, S and O,
(3) cyclohexane,
(4) —C 1-3 alkyl-heteroaryl,
(5) —C 1-3 alkyl-heterocycle,
wherein choices (1) through (5) are optionally substituted with 1 or 2 groups selected from
(1) oxo,
(2) CH 3 ,
(3) OH,
(4) —CH(OH)CH 3 ,
(5) —OCH 3 ,
(5) —C(O)—CH 3 ,
(6) —C(O)—O—C-(t-butyl),
(7) —C(O)NHCH 3 ,
(8) C(O)N(CH 3 ) 2 ,
(10) —NH 2 ,
(11) —N(CH 3 ) 2 ,
(12) AR′, wherein AR′ is selected from the group consisting of
8 . A compound according to claim 7 wherein
R is selected from the group consisting of
9 . A compound which is selected from the group consisting of:
Ex. #
R
X
A
F
B
F
C
F
D
F
E
F
F
F
G
F
H
F
I
F
J
F
K
F
L
F
M
F
N
F
O
F
P
F
Q
F
R
F
S
F
T
F
U
F
V
F
W
F
X
F
Y
F
Z
F
A1
F
B1
F
C1
F
D1
F
E1
F
F1
F
G1
F
H1
F
I1
F
J1
F
K1
F
L1
F
M1
F
N1
F
O1
F
P1
F
Q1
F
R1
F
S1
F
T1
F
U1
F
V1
F
W1
F
X1
F
Y1
F
Z1
F
A2
F
B2
F
C2
F
D2
F
E2
F
F2
F
G2
F
H2
F
I2
F
J2
F
K2
F.
10 . A pharmaceutical composition which comprises an inert carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.
11 . A method for the manufacture of a medicament for antagonizing the effect of substance P at its receptor site or for the blockade of neurokinin-1 receptors in a mammal comprising combining a compound of claim 1 or a pharmaceutically acceptable salt thereof with a pharmaceutical carrier or diluent.
12 . A method for the manufacture of a medicament for the treatment of a physiological disorder associated with an excess of tachykinins in a mammal comprising combining a compound of claim 1 or a pharmaceutically acceptable salt thereof with a pharmaceutical carrier or diluent.Cited by (0)
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